TANDEM: Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies

Sponsor

NewAmsterdam Pharma (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06005597

Collaborator

(none)

400

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The study is a placebo-controlled, double-blind, randomized, phase 3 study in participants with heterozygous familial hypercholesterolemia (HeFH) and/or atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors to evaluate the efficacy, safety and tolerability of obicetrapib 10mg and ezetimibe 10mg fixed dose combination as an adjunct to diet and maximally tolerated lipid-lowering therapy.

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemias Hypercholesterolemia Familial Hypercholesterolemia ASCVD High Cholesterol	Combination Product: Combination Therapy Drug: Monotherapy obicetrapib Drug: Monotherapy ezetimibe Other: Combination Therapy placebo Other: Obicetrapib Placebo Other: Ezetimibe Placebo	Phase 3

Detailed Description

This study will be a placebo-controlled, double-blind, randomized, phase 3 study in participants with heterozygous familial hypercholesterolemia (HeFH) and/or atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy. The screening period for this study will take up to 14 days. Afterwards patients will be randomized 1:1:1:1 to Obicetrapib 10 mg and ezetimibe 10 mg fixed dose combination, obicetrapib 10 mg, ezetimibe 10 mg or placebo for a 84 day treatment period. After the treatment period, patients will have an end of study follow-up visit.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Placebo-controlled, double blind, randomizedPlacebo-controlled, double blind, randomized

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

placebo tablets made to resemble active; placebo capsule made to resemble active

Primary Purpose:

Treatment

Official Title:

A Placebo-Controlled, Double-Blind, Randomized, Phase 3 Study to Evaluate the Effect of Obicetrapib 10 mg and Ezetimibe 10 mg Fixed Dose Combination Daily on Top of Maximally Tolerated Lipid-Modifying Therapy in Participants With Heterozygous Familial Hypercholesterolemia (HeFH) and/or Atherosclerotic Cardiovascular Disease (ASCVD) or Multiple ASCVD Risk Factors

Anticipated Study Start Date :

Jan 1, 2024

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination Therapy once-daily obicetrapib 10 mg and ezetimibe 10 mg fixed dose combination tablet, placebo tablet, placebo capsule	Combination Product: Combination Therapy tablet; 10mg obicetrapib and 10mg ezetimibe fixed does combination Other Names: Cholesteryl ester transfer protein (CETP) inhibitor obicetrapib ezetimibe Other: Obicetrapib Placebo tablet; no active ingredient Other: Ezetimibe Placebo capsule; no active ingredient
Experimental: Monotherapy obicetrapib once-daily obicetrapib 10 mg, placebo tablet, placebo capsule	Drug: Monotherapy obicetrapib tablet; 10mg obicetrapib Other Names: CETP inhibitor Other: Combination Therapy placebo tablet; no active ingredient Other: Ezetimibe Placebo capsule; no active ingredient
Active Comparator: Monotherapy ezetimibe once-daily ezetimibe 10 mg capsule, 2 placebo tablets	Drug: Monotherapy ezetimibe capsule; 10mg ezetimibe Other: Combination Therapy placebo tablet; no active ingredient Other: Obicetrapib Placebo tablet; no active ingredient
Placebo Comparator: Placebo once-daily placebo tablets (2), placebo capsule	Other: Combination Therapy placebo tablet; no active ingredient Other: Obicetrapib Placebo tablet; no active ingredient Other: Ezetimibe Placebo capsule; no active ingredient

Outcome Measures

Primary Outcome Measures

Effect of combination therapy compared to placebo on LDL-C [84-Days]
Percent Change in LDL-C
Effect of combination therapy compared to ezetimibe 10 mg monotherapy on LDL-C [84-Days]
Percent Change in LDL-C
Effect of combination therapy compared to obicetrapib 10 mg monotherapy on LDL-C [84-Days]
Percent Change in LDL-C

Secondary Outcome Measures

Effect of combination therapy compared to placebo on non-HDL-C [84-Days]
Percent Change in non-HDL-C
Effect of combination therapy compared compared to ezetimibe 10 mg monotherapy on non-HDL-C [84-Days]
Percent Change in non-HDL-C
Effect of combination therapy compared to obicetrapib 10 mg monotherapy on non-HDL-C [84-Days]
Percent Change in non-HDL-C
Effect of combination therapy compared to placebo on Apolipoprotein B (ApoB) [84-Days]
Percent Change in ApoB
Effect of combination therapy compared to ezetimibe 10 mg monotherapy on ApoB [84-Days]
Percent Change in ApoB
Effect of combination therapy compared to obicetrapib 10 mg monotherapy on ApoB [84-Days]
Percent Change in ApoB

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Have underlying HeFH and/or a history of ASCVD or multiple ASCVD risk factors
On maximally tolerated lipid-modifying therapy as an adjunct to a diet and lifestyle modifications
LDL-C ≥ 70 mg/dL or HDL-C ≥ 100 mg/dL
Triglycerides < 500
Estimated glomerular filtration rate ≥ 15 mL/min/1.73 m2

Exclusion Criteria:

History of New York Heart Association (NYHA) class III or IV heart failure of left ventricular ejection fraction <30%
Hospitalized for heart failure within the last 5 years
Myocardial infarction, stroke, non-elective coronary revascularization or hospitalization for unstable angina or chest pain in the last 3 months
Uncontrolled severe hypertension
Diagnosis of homozygous FH
Liver disease
HbA1c ≥ 10.0% or fasting glucose ≥ 270 mg/dL
Thyroid-stimulating hormone >1.5 x upper limit of normal (ULN)
History of malignancy
Creatinine kinase (CK) >3 X ULN
Alcohol abuse
Treatment with investigational product
Treatment with gemfibrozil or ezetimibe
Previous participation in a trial evaluating obicetrapib
Known allergy to study drugs, placebo or excipients in study drugs of placebo
Other condition that would interfere with the conduct of the study